Immunohistochemical and ultrastructural studies in a patient with a Kindler syndrome-like disorder

Kindler syndrome is an autosomal recessive genodermatosis characterized by trauma-induced acral skin blistering from infancy, photosensitivity, generalized poikiloderma, and diffuse cutaneous atrophy. Mutations in the KIND1 gene that encodes for the focal contact-associated protein kindlin-1 have been identified in several patients although the spectrum of clinical abnormalities is protean and genetic heterogeneity is plausible. A 32-year-old Japanese male, born to consanguineous parents, presented with acral skin blistering, cutaneous atrophy, palmoplantar thickening, finger contractures, absence of dermatoglyphics, and nail dystrophy. He also had leukoplakia of the tongue but did not report photosensitivity or show signs of poikiloderma. A biopsy taken from bullous atrophic skin on the dorsal surface of his left hand showed sub-epidermal blistering, vacuoles within basal keratinocytes and immunohistochemical evidence of basement membrane reduplication. Intensity of Kindlin-1 expression in patient skin was indistinguishable from that in normal skin. Electron microscopy demonstrated multiple tubulo-vesicular structures and electron dense amorphous keratinocyte-derived material immediately below the dermal-epidermal junction. Mutational analysis of the KIND1 gene failed to identify any pathogenic mutation(s). Although this patient’s clinical and skin biopsy features appear to match the clinico-pathological criteria for a diagnosis of Kindler syndrome, no mutation in KIND1 was detected. This suggests genetic heterogeneity in this genodermatosis or perhaps the existence of a subset of patients that have a distinct but currently unclassified related inherited disorder. Identification of similar patients and characterization of this Kindler-like syndrome is expected to provide new insight into clinical disorders associated with structural pathology within the cutaneous basement membrane zone